Dejstvo melatonina na regulaciju noradrenalinske neurotransmisije u mozgu, srcu i nadbubrežnim žlezdama u animalnom modelu depresije

Abstract

The hippocampus is a brain structure highly sensitive to stress. Melatonin plays a role in maintaining the circadian rhythm, and its antioxidant properties have been confirmed. Chronic mild unpredictable stress (CUMS) is an animal model that mimics the role of chronic stress in the development of depression in humans. This model has been accepted as a paradigm that replicates many of the behavioral disorders that accompany depression. Male Wistar rats were exposed to CUMS for 4 weeks. During that period, the animals were treated with melatonin at a dose of 10 mg/kg body weight, i.p. Behavioral parameters were monitored in the open field test, elevated plus maze and the forced swim test. CUMS resulted in prolonged immobility in the forced swim test. Treatment of rats with melatonin reduced immobility compared to the control group, exhibiting an antidepressant effect. Melatonin normalized the amount of noradrenaline by acting on degradation enzymes and the VMAT2 transporter in the hippocampus. This study showed that melatonin exhibits antidepressant effects in an animal model of depression. In the open field test, animals treated with melatonin spent more time in the center of the arena, indicating its anxiolytic effect. Our results showed decreased gene expression for α1-, α2- and β2-adrenoreceptor in the hippocampus of stressed rats, while there was no change in gene expression for β1-adrenoreceptor. Melatonin treatment in CUMS rats prevented stress-induced decreases in α1- and β2-adrenoreceptor mRNA and protein levels, while not affecting β1- and α2-adrenoreceptor mRNA and protein levels. Reduction of catecholamine biosynthesis and enhancement of their reuptake in the adrenal medulla of rats exposed to CUMS is associated with the beneficial effects of chronic melatonin treatment. The observed beneficial effects of melatonin in the heart via enhanced uptake and reduced degradation are most likely compensatory mechanisms that protect cardiomyocytes from the deleterious effects of excessive noradrenaline stimulation. The obtained results contribute to a better understanding of the molecular mechanisms of action of melatonin by monitoring changes in the expression of genes responsible for the process of synthesis, uptake and storage of catecholamines in the brain, cardiovascular system and medulla of the adrenal glands as sites of primary synthesis of catecholamines.